Role of dopamine transporter imaging in routine clinical practice

Abstract

Functional imaging of the dopamine transporter (DAT) defines integrity of the dopaminergic system and has its main clinical application in patients with mild, incomplete, or uncertain parkinsonism. Imaging with specific single positron emission computerised tomography ligands for DAT (FP-CIT, beta-CIT, IPT, TRODAT) provides a marker for presynaptic neuronal degeneration. Striatal uptake correlates with disease severity, in particular bradykinesia and rigidity, and monitoring of progression assists in clinical trials of potential neuroprotective drugs. DAT imaging is abnormal in idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy and does not distinguish between these disorders. Dopamine loss is seen even in the earliest clinical presentations of true parkinsonism; a normal scan suggests an alternative diagnosis such as essential tremor, vascular parkinsonism (unless there is focal basal ganglia infarction), drug-induced parkinsonism, or psychogenic parkinsonism. Congruence between working clinical diagnosis and DAT imaging increases over time in favour of baseline DAT imaging results. Additional applications are characterising dementia with parkinsonian features (abnormal results in dementia with Lewy bodies, normal in Alzheimer's disease); and differentiating juvenile-onset Parkinson's disease (abnormal DAT) from dopa-responsive dystonia (normal DAT).

Quantification of Dopamine Transporter Binding Using [18F]FP-β-CIT and Positron Emission Tomography

“…The most common DAT ligand is b-CIT, a cocaine analogue, which has been labelled with radionuclides for both PET ( 124 I; Coenen et al, 1995) and SPECT, ( 123 I; Neumeyer et al, 1991;Laruelle et al, 1994;Coenen et al, 1995;Marshall and Grosset, 2003). Especially SPECT tracers often have been used for clinical purposes.…”

Parkinson's disease – pathology, aetiology and diagnosis

“…106 SPECT scanning may also be a sensitive early diagnostic marker for presynaptic parkinsonism versus non-parkinsonian tremor disorders such as essential tremor, as well as drug-induced parkinsonism and vascular parkinsonism. 109 Presynaptic cerebrovascular lesions may cause 'punched out' areas of poor uptake on SPECT scanning and result in an abnormal scan which differs from the pattern seen in PD. For a review of dopaminergic imaging in parkinsonism, see Kemp (2005).…”

Rotation Radius Dependence of 123I-FP-CIT and 123I-IBZM SPECT Uptake Ratios: A Monte Carlo Study

“…As in previous studies (19)(20)(21), the densities of the different brain structures were set to 1.04 g/cm 3 for brain tissue, 1.30 g/cm 3 for the skull (average bone density according to the International Commission on Radiological Protection (22)), and 0.60 g/cm 3 for the low-density regions (mouth cavity and sinuses) (23). For simulations of the high uptake ratio, corresponding to uptake of 123 I-FP-CIT for a healthy subject, the relative activity concentrations were set to 16 in the striatal structures and 3 in the rest of the brain.…”

“…The most commonly used radioligand for dopamine transporter SPECT, 123 I-FP-CIT ( 123 I-N-v-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane, or 123 I-ioflupane [DaTscan; GE Healthcare B.V.]), has affinity to the presynaptic dopamine transporter protein in the striatum. This characteristic has been shown to be useful for differentiating idiopathic Parkinson disease from essential tremor (2), idiopathic parkinsonism, and drug-induced parkinsonism (3)(4)(5). Striatal uptake of 123 I-FP-CIT is reduced in idiopathic Parkinson disease patients, compared with healthy controls, and can be very low in advanced stages of the disease.…”

“…Striatal uptake of 123 I-FP-CIT is reduced in idiopathic Parkinson disease patients, compared with healthy controls, and can be very low in advanced stages of the disease. The radiopharmacon 123 I-IBZM ( 123 I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[1-ethyl-2-pyrrodinyl)-methyl]benzamide [ 123 I-Iolopride; GE Healthcare B.V.]) is a dopamine receptor antagonist that has a high affinity to D 2 -and D 3 -receptors (6,7). 123 I-IBZM SPECT is claimed to have a differential diagnostic value in the issue of idiopathic Parkinson disease or atypical parkinsonism (i.e., multiple-system atrophy or progressive supranuclear palsy) (8,9).…”